Predictors of long-term survival after valve
replacement for chronic aortic regurgitation
Is M-mode echocardiography sufficient?
R. Corti
1, C. Binggeli
1, M. Turina
2, R. Jenni
1, T. F. Lu
¨ scher
1and J. Turina
11Division of Cardiology and2Clinic for Cardiovascular Surgery,University Hospital, Zurich, Switzerland
Aims The clinical importance of pre-operative and follow-up echocardiographic studies in patients operated on for chronic severe aortic valve regurgitation is still a matter of debate. The prognostic significance of M-mode echocardiography has never been directly compared with clinical and angiographic data.
Methods and Results Univariate and multivariate
analyses of cumulative survival were performed for clinical, echocardiographic and angiographic data of 125 patients operated on between 1975 and 1983, and followed for 13·36·4 years. Ten and 20 year survival rates were 77% and 48%, respectively. Age, NYHA class, angiographic volumes, ejection fraction, as well as M-mode echocardio-graphic end-systolic dimension and shortening fraction were the main pre-operative prognostic parameters for long-term survival. In a multivariate analysis the angio-graphic end-systolic volume index, age and pre-operative NYHA class were independent pre-pre-operative prognostic variables of long-term survival. A postoperative reduction in end-diastolic dimension of >20% predicted a
significantly better late survival (74% vs 44% after 20 years,
P<0·001).
Conclusions Age, pre-operative NYHA class and left
ventricular systolic function are the main determinants of long-term survival after valve replacement for chronic aortic regurgitation. Despite a slightly lower predictive value of echocardiography when compared to angiography, it appeared sufficient for everyday clinical decision making for valve replacement. Echocardiography within 6 months postoperatively is able to detect recovery of left ven-tricular function, and enables additional risk-stratification, regardless of pre-operative findings.
(Eur Heart J 2001; 22: 866–873, doi:10.1053/euhj.2000.2314)
2001 The European Society of Cardiology
Key Words: Aortic regurgitaton, echocardiography,
prognosis, valves, valve replacement, angiography.
See page 808 for the Editorial comment on this article
Introduction
Chronic aortic regurgitation is a slowly progressive disease with a long asymptomatic period and rapid deterioration when symptoms develop[1–6]. It is generally
accepted that valve replacement is mandatory in symp-tomatic patients with severe chronic aortic regurgi-tation[5]. Despite some controversies, there is a general
consensus that valve replacement for chronic severe aortic regurgitation should be performed even in asymp-tomatic or mildly sympasymp-tomatic patients before a con-siderable decrease in systolic function and severe
enlargement of the left ventricle ensue[5,7,8]. The surgical
results are poor when valve replacement is postponed until symptoms are severe or myocardial dysfunction is marked[9–12]. The best predictive parameter for
post-operative outcome is still a matter of debate. However, the influence of pre-operative parameters on the true ‘long-term’ prognosis is scarcely known because most reports are based on relatively short follow-up (<5 years)[10,11,13–17]. During the last 20 years, beside
symp-toms and quantitative angiography, the prognostic value of echocardiography has been of particular interest because this non-invasive method is an ideal clinical tool for diagnosis and monitoring of chronic aortic regurgitation.
Surprisingly, the predictive value of echocardiography and the ‘standard’ invasive method of quantitative angiography have never been properly compared. In this study, we compared the predictive value of
Revision submitted 10 June 2000, and accepted 21 June 2000.
Correspondence: Juraj Turina, MD, Cardiology, University
pre-operative M-mode echocardiography and quantita-tive left ventricular angiography for long-term outcome after valve replacement for chronic aortic regurgitation. Besides pre-operative echocardiography, the prognostic value of early postoperative echocardiography was also evaluated.
Patients and Methods
We studied 125 patients who underwent aortic valve replacement for chronic aortic regurgitation between 1975 and 1983. All patients underwent pre-operative clinical assessment, cardiac catheterization, quantitative left ventricular angiography, and M-mode echo-cardiography. The patient population represents 90% (125/139) of all available patients at our institution. Patients with acute endocarditis, coronary artery disease, more than a trivial aortic stenosis (aortic valve opening area <1·5 cm2) or mitral valve disease were
excluded. Patients reported here were part of a larger study about predictive parameters of survival after extended follow-up after valve replacement in chronic aortic regurgitation[18]. The main characteristics of the
patients are presented inTable 1. The age of the patients at the time of operation ranged from 18 to 73 years (mean 4413 years), 109 (87%) were male and 16 female. Symptoms and functional impairment,
accord-ing to the New York Heart Association (NYHA), were assessed at the time of operation regardless of previous symptoms or history. Mean NYHA class was 2·30·8: 14% of patients were in class I, 52% in class II and 30% in class III.
Cardiac catheterization and angiography
All patients underwent right and left heart catheteriz-ation and cineangiography. Coronary arteriography was performed in all patients older than 45 years or in the presence of angina pectoris. The angiographic left ven-tricular end-diastolic volume index, end-systolic volume index and left ventricular ejection fraction were calcu-lated by the area–length method from monoplane and, since the end of 1976 from biplane cineangiograms. The severity of valve regurgitation was estimated by angiography.
Echocardiography
Echocardiographic recordings were obtained by a 2·2 MHz single beam transducer (Cardiovisor, Organon Teknika), with simultaneous recording of the ECG and phonocardiogram. All recordings and measurements were performed by two experienced physicians (R.J. and J.T.). Only high quality echocardiography tracings were accepted. The end-diastolic dimension was measured at the peak of the R-wave in the ECG, and the end-systolic dimension at the beginning of the second sound on the phonocardiogram. The majority of the patients (n=85) also underwent early postoperative (3–6 months after valve replacement), and a minority (n=35) late post-operative (mean 3·3 years, range 1–10 years) echo-cardiography at our institution. These 85 patients are representative of the entire collective with respect to pre-operative characteristics and postoperative survival (10 years survival 81% vs 78% in patients who survived the first 6 months but did not have postoperative echocardiography). The postoperative changes of the left ventricular end-systolic dimension and end-diastolic dimension, respectively, are expressed as a percentage of the pre-operative value. The echocardiographic left ventricular volume was calculated using the Teichholz formula (volume=(7.0/(2.4+D))D3; D means
echo-cardiographic left ventricular dimension) and corrected for the body surface area[19]. Correlation between
echocardiographic and angiographic left ventricular vol-umes was relatively good, especially for only moderately increased volumes (correlation coefficient r=0·67,
Fig. 1). Correlation was less than optimal in patients
with very large ventricles, mainly due to considerable under-estimation of the left ventricular volume by echocardiography in some patients (Fig. 1).
Surgical procedures
Different mechanical (n=78, 62%) and biological (n=47, 38%) prostheses were used. The Bjo¨rk–Shiley valve Table 1 Baseline characteristics of the study population
(n=125)
Variable MeansSD Range
Age (years) 44·313 18–73
Gender (male/female) 109/16
Heart rate (beats . min1) 74·116·6 45–142
NYHA class 2·260·75 I/II/III/IV 17/65/37/6 Sinus rhythm 92% CI (l . min1. m2) 3·090·72 1·7–5 EDP (mmHg) 18·910·9 5–65 LV angiography EDVI (ml . m2) 217·2867·02 114–503 ESVI (ml . m2) 101·851·2 25–354 EF (%) 54·810·6 30–78 AR (%) 60·213·1 45–84 LV echocardiography EDD (cm) 7·861·02 5·5–10·5 EDVI (ml . m2) 18754 77–355 ESD (cm) 5·431·02 3·19–7·74 ESVI (ml . m2) 8237 27–183 Sh (%) 31·128·17 12–51 PWT (cm) 1·10·2 0·8–1·6 EDD/2*PWT index 3·520·73 1·8–6·6
CI=cardiac index; EDP=end-diastolic pressure; LV=left ventricle; EDVI=end-diastolic volume index; ESVI=end-systolic volume index; EF=ejection fraction; AR=aortic regurgitant fraction;
EDD=end-diastolic diameter; ESD=end-systolic diameter;
Sh=shortening fraction; PWT=posterior wall thickness;
(n=72, 58%) was the most frequently implanted mech-anical prosthesis and the Carpentier–Edwards (n=35, 28%) was the most frequently implanted bioprosthesis. In 22 cases, additional surgical procedures were neces-sary because of aneurysmatic dilatation of the ascending aorta. Different types of intra-operative myocardial pro-tection were used between 1975 and 1978; after 1978 hypothermic potassium cardioplegia and pericardial irrigation became the standard method of myocardial protection[18].
Follow-up
After surgery, all patients were seen at least once in our outpatient clinic. Additional information was obtained with standardized questionnaires mailed to patients and their physicians. Causes of death and cardiac compli-cations were obtained from medical reports, death cer-tificates, and telephone contact with physicians. These data were classified according to recommended guide-lines[20]. All deaths related to heart failure, rhythm
disturbancies, reoperations, prosthesis and prosthesis-related treatment as well as all sudden and otherwise unexplained deaths were classified as cardiac. The mean follow-up was 13·36·4 years (1662 patients-years), 17·4 years in surviving and 8·3 in deceased patients. Follow-up was incomplete in eight patients lost 28–172 months (mean 105) after valve replacement.
Statistical analysis
Statistical evaluations and all calculations were per-formed with StatView 4.5 software (Abacus Concepts, Inc). Continuous data are presented with 1 standard deviation (SD). Survival was calculated according to
the Kaplan–Meier method, the survival curves were compared with the log rank test (Mantel–Cox), P<0·05 was considered as statistically significant. Patients who underwent reoperation during follow-up were retained in the statistical calculation. Univariate analysis of general and cardiac survival was performed separately for each pre-operative clinical, angiographic and echocardiographic parameter. Multivariate analysis was applied stepwise using the Cox proportional hazard model to all significant parameters in the univariate analysis. The relationship between angiographic and echocardiographic volumetric data was evaluated by correlation analysis and presented as the linear corre-lation. The pre-operative and postoperative echocardio-graphic values were compared by Student’s t-test for paired samples.
Results
Survival
Operative mortality (<30 days after surgery) was 3·9% (5/125). During follow-up 49 patients died, operative death included. Thirty six patients (73%) died of cardiac causes; heart failure (n=14) and sudden death (n=9) were the most frequent causes of cardiac death. Other cardiac deaths included stroke (n=5), endocarditis (n=2), arrhythmias (n=2), aortic dissection (n=2), cor-onary artery disease (n=1), and reoperation (n=1). Cumulative general and cardiac survival is shown
in Fig. 2. Survival rate at 5, 10, 15 and 20 years was
88%, 77%, 65%, 48%, respectively. The mortality rate remained almost stationary during the entire follow-up (2·5%/pat-year). During follow-up, 38 patients under-went reoperation, mainly (68%) due to the degeneration of bioprostheses. At the end of follow-up, 80% of the surviving patients were in NYHA classes I or II.
Pre-operative survival parameters
The prognostic significance of different clinical, angio-graphic and echocardioangio-graphic pre-operative par-ameters on long-term survival is summarized inTable 2. Univariate analysis was performed separately for general and cardiac survival. Older age at operation, higher NYHA class, higher angiographic end-systolic volume index and end-diastolic volume index, lower ejection fraction, higher echocardiographic end-systolic dimension and end-systolic volume index and in part lower shortening fraction (%Sh) and end-diastolic dimension/2*PWT (PWT: posterior wall thickness) were negative predictors of long-term survival in the univari-ate analysis. The results of the analysis for general and cardiac survival were very similar. Predictive value of all angiographic and echocardiographic parameters was higher when the data were analysed as continues than as nominal values (Table 2). In a multivariate stepwise
0 250 350 Echocardiographic ESVI (ml.m2) y = 0·85x + 29·6 R = 0·67 Angiographic ESVI (ml.m 2 ) 50 100 150 200 250 300 50 100 150 200
Figure 1 Correlation of angiographic and echocardio-graphic volume. The echocardioechocardio-graphic volume was calculated using the Teichholz formula corrected for body surface area. ESVI=end-systolic volume index.
analysis age, pre-operative NYHA class and angio-graphic end-systolic volume index were independent predictive parameters for long-term cardiac survival (Table 3).
Early postoperative echocardiography
The course of left ventricular dimension assessed by echocardiography is shown in Fig. 3. The echocardio-graphic pre-operative end-diastolic dimension decreased significantly in the early postoperative (3 to 6 months) follow-up (7·81·0 to 6·11·0 cm, P<0·0001) and
did not change significantly later on (6·11·0 to 6·11·4 cm, ns). Similarly, the echocardiographic-end-systolic dimension decreased early postoperation (5·41·0 to 4·31·2 cm, P<0·0001) and remained unchanged during the late follow-up (4·31·2 to 4·21·5 cm, ns). Surviving patients had a progressive decrease in left ventricular dimensions during follow-up: 25% and 42% at <6 months and 3·3 years, respectively. The reduction in postoperative cardiac dimensions was smaller in those patients who died from cardiac causes compared to surviving patients (16·6% vs 23·7%,
P<0·05). The posterior wall thickness (1·10·2 cm) and
0 20 100 Time (years) n = 125 Cumulative survival (%) 10 20 30 40 50 60 5 10 15 70 80 90 n = 108 n = 91 76% 88% n = 61 65% n = 10 48%
Figure 2 Cumulative general and cardiac survival. The number of patients under study and survival rates at 5, 10, 15 and 20 years are indicated. =cardiac survival; =general survival.
Table 2 Univariate analysis of prognostic parameters for general and cardiac survival
General survival Cardiac survival Pre-op Early post-op Pre-op Early post-op
NYHA class 0·004 0·01 I/II vs III/IV 0·001 0·01 Angiography EDVI 0·003 0·01 <200 vs >200 ml . m2 0·004 0·004 ESVI 0·0002 0·001 <120 vs >120 ml . m2 0·01 0·004 EF 0·02 0·007 d55 vs <55% 0·07 0·01 Echocardiography EDD 0·2 0·01 0·01 0·002 <75 vsd75 mm 0·3 0·02 0·02 0·03 ESD 0·03 0·001 0·01 0·0003 <55 vsd55 mm 0·09 0·02 0·07 0·04 Sh (%) 0·06 0·007 0·04 0·01 c25 vs >25% 0·01 0·03 0·02 0·02 EDVI 0·1 0·03 0·1 0·001 ESVI 0·04 0·003 0·03 0·002
EDVI=end-diastolic volume index; ESVI=end-systolic volume index; EF=ejection fraction; EDD=end-diastolic diameter; ESD=end-systolic diameter; Sh %=shortening fraction.
%Sh (319%) did not significantly change during the follow-up.
Patients whose left ventricular diastolic and systolic dimensions were reduced early postoperation had a better long-term survival. In the univariate analysis of early postoperative echocardiographic left ventricular parameters for long-term survival (Table 2) higher systolic dimension, systolic volume index, end-diastolic dimension and lower %Sh were statistically significantly related to a less successful late survival. Early postoperative echocardiographic findings (3 to 6 months after valve replacement) had a significantly higher prognostic influence on long-term outcome than pre-operative echocardiographic data. The highest prognostic significance was end-systolic volume index, end-diastolic volume index and end-systolic dimension (Table 2). Patients with an early postopera-tive reduction of the end-diastolic dimension >20% have a significantly better cardiac and general survival (at 20 years: 74% vs 44% in those with a reduction <20%,
P<0·001 for trend) (Figs 4 and 5). During the later follow-up, death due to heart failure and sudden death were registered mainly in patients with an early post-operative reduction of end-diastolic dimension <20%.
Discussion
In severe chronic aortic regurgitation, symptoms and left ventricular systolic function are the main predictors of early and late outcome after valve replacement[11–14,21].
Today, very low operative mortality and good long-term survival make valve replacement for severe aortic regurgitation mandatory even in mildly symptomatic or asymptomatic patients before left ventricular systolic function decreases and systolic dimensions are greatly enlarged[5,8,18,22]. Quantitative left ventricular
angio-graphy and echocardioangio-graphy are standard, generally accepted methods for assessment of left ventricular function in chronic aortic regurgitation and of utmost importance for optimal timing of valve replacement[22].
Interestingly, despite more than 25 years experience with echocardiography and angiography, the predictive value of both methods for outcome after valve replacement in aortic regurgitation has not been directly compared.
In our study, we compared the predictive value of pre-operative echocardiographic and angiographic data for extended outcome after aortic valve replacement in chronic aortic regurgitation. Low operative mortality and good long-term survival in the study compared favourably with published reports[1,23–25]. Heart failure
and sudden death were the main causes of postoperative death even at prolonged follow-up. Data presented here are representative of the experience in our institution on valve replacement for chronic aortic regurgitation in the late 1970s and early 1980s[18]. More than 90% of all
consecutive patients with aortic regurgitation, who underwent valve replacement during that period, were included and neither the outcome nor the predic-tive value of different pre-operapredic-tive clinical, haemo-dynamic or angiographic parameters in this study dif-fered essentially from the entire group of patients[18].
Availability of high quality echocardiograms, conducted Table 3 Independent predictors of cardiac survival on
long-term follow-up in multivariate, stepwise analysis
Parameter P Exp (Coef)
Age <0·0001 1·054
NYHA 0·05 1·226
ESVI 0·0008 1·01
Exp (Coef)=exponential coefficient; ESVI=end-systolic volume
index. 3 9 Dimension (cm) 4 5 6 7 8 Pre-operative Early postoperative (< 6 months) n = 125 n = 85 ESD EDD P = 0·0001 * *
Figure 3 The course of echocardiographic systolic (ESD) and diastolic dimension (EDD) from pre-operative to early postoperative (<6 months). =surviving patients; =cardiovascular deaths. Mean values and 1 standard deviation (SD) are shown, statistical significance is indi-cated for all groups of data; *=significant difference between cardiac death and surviving patients (P<0·0001).
0 20 100 Time (years) n = 85 Cumulative survival (%) 10 20 30 40 50 60 5 10 15 70 80 90 n = 38 n = 30 n = 29 n = 39 n = 19 n = 15 P < 0·001
Figure 4 Cumulative survival of 85 patients with post-operative echocardiographic examination. Patients are divided according to the reduction of the postoperative end-diastolic dimension (EDD) in relation to the pre-operative value. =early postpre-operative reduction of EDD >20%; =the reduction of EDD <20%. Significance for trend was evaluated by log rank test in Mantel–Cox analysis.
in a prospective manner, was the only criterion for inclusion of the patients in the study.
Study limitations
Some caution is necessary in the interpretation of cine-angiographic studies and in particular echocardiograms performed 20 years earlier. Quantitative angiography was performed by the area length method, mostly from biplane left ventricular angiograms, which even today are considered to be the gold standard for volumetric calculations. Hence, these data must be considered as representative. In the 1970s and early 1980s only M-mode echocardiography was available. Hence, only the short axis of the left ventricle could be obtained for volumetric calculations. Measurements of left ventricu-lar dimensions with M-mode were less than optimal when compared to 2D-echocardiography supported measurements used today, but still satisfactory. The correlation of our non-simultaneously performed angio-graphic and echocardioangio-graphic volumetric data is fair but, as expected, the variation is considerable in patients with very large left ventricles[26]. Different formulas for
the calculation of M-mode echocardiographic volume have never been validated in chronic aortic regurgitation where the enlargement of the ventricle is more ellipsoid than spherical. As shown in this study, the Teichholz formula achieves an acceptable correlation between echocardiography and angiography in moderately enlarged left ventricles, but considerable
under-estimation of the volume with echocardiography, how-ever, is seen in some patients with very large ventricles. The calculation of left ventricular volumes from M-mode data is not necessary because these do not improve the predictive value of echocardiography and are today obsolete.
Prognostic value of pre-operative
echocardiography and angiography
The systolic volume or dimension, respectively, and systolic function expressed as ejection fraction and short-ening of left ventricular dimensions had, beside age and symptoms, the highest singular predictive value of differ-ent angiographic and echocardiographic parameters. This confirms many previous reports based on much shorter postoperative follow-up[8,10–13,15,21,23,27–29]. The
angiographic and echocardiographic systolic volumes and dimensions are better predictors of postoperative outcome than those obtained at diastole[12,18,21]. For
daily clinical practice, M-mode echocardiographic dimensions seem to be sufficient for determination of left ventricular function. Indeed, more sophisticated volume calculations do not increase the predictive value of echocardiography. In the univariate analysis, angio-graphic parameters had higher predictive value than M-mode echocardiographic parameters and that is why in multivariate stepwise analysis angiographic parameters override those of echocardiography.
–60 11 10 Pre-operative EDD (cm) Change in EDD (%) 5 –50 –40 –30 –20 –10 0 8 9 10 7 6
Figure 5 Changes in end-diastolic dimension (EDD) are represented as
a function of the pre-operative EDD value. =surviving patients;
=patients who died during the follow-up (sudden cardiac death or heart failure); *=other cardiovascular death: arrhythmia, endocarditis,
The prognostic importance of pre-operative left ventricular function for postoperative survival became really evident and increased continuously with extension of follow-up. Some controversies concerning the prog-nostic value of pre-operative echocardiography can be resolved by this long-term follow-up. In patients with severely enlarged left ventricular dimensions and decreased function, an insufficient reduction in size and an insufficient increase in function was uniformly seen by all authors[22]. A reduced survival of patients with
pre-operative severely enlarged left ventricles was found only in studies with a relatively high operative and early postoperative mortality[10,11,22]. Today, improved
surgical techniques and intra- and peri-operative management of these patients allow excellent survival without excess early mortality, even in patients with pre-operatively severely impaired myocardial func-tion[1,17,23,30,31]. In our study, patients who survived the
operation but did not achieve a sufficient improvement of myocardial function remained exposed to a high risk of cardiac death and their long-term prognosis was less favourable. Cardiac death remains the main cause of attrition even 20 years after valve replacement; the proportion of patients dying of non-cardiac or strictly prosthesis-related causes was relatively low.
Prognostic value of early postoperative
echocardiography
Early postoperative echocardiography was an important predictor of late outcome, which enabled further prog-nostic differentiation of the patients. Within the first weeks and months of valve replacement, considerable reduction of left ventricular size and improvement of myocardial function ensue[15,32,33]. Later on, only minor
changes in myocardial function occur. A marked decrease of left ventricular diastolic dimensions (>20% of pre-operative value) was associated with a signifi-cantly better long-term survival, even in patients with pre-operative severely enlarged ventricles. Elimination of volume overload by valve replacement leads to considerable improvement of systolic function in chronic aortic regurgitation in a great majority of patients[15,16,27,32]. Rearrangement of myofibrils without
intrinsic myocyte damage occurs in enlarged but other-wise ‘normal’ left ventricles without contractility deficit under severe chronic volume overload[34]. As our data
demonstrate, especially in patients with insufficient early postoperative reduction of left ventricular size, heart failure or sudden death occurred late after valve replace-ment. Sufficient contractile function can be maintained over years even in patients with severely reduced myo-cardial function, and that is why only after very long follow-up can statistically significant differences in survival patterns be demonstrated. Echocardiography within 6 months of operation is able to detect recovery of left ventricular function, thus enabling additional risk-stratification of patients, regardless of pre-operative
findings. Whether treatment with ACE inhibitors early after valve replacement can improve late outcome is unknown, although pre-operatively a 15–20% reduction of left ventricular dimensions has been described after 12 months therapy with quinapril[35]. None of our
patients was treated with ACE inhibitors early post-operatively because these drugs were not available in the 1970s and early 1980s. At the end of the study, in the late 1990s, only 22% of our patients were on ACE inhibitors.
Summary and prospects for future
handling
Pre-operative systolic left ventricular function, as assessed by left ventricular angiography and/or echocar-diography is, besides age and symptoms, a major prog-nostic factor of late outcome after valve replacement in chronic aortic regurgitation. The prognostic value of pre-operative quantitative, biplane left ventricular angiography is superior to M-mode echocardiography. However, this disadvantage of echocardiography is more than offset by its non-invasive nature and the possibility of repeated monitoring of myocardial func-tion. The good prognostic value of early postoperative changes in left ventricular dimensions considerably in-creases the clinical importance of echocardiographic monitoring in these patients. Thus, in severe chronic aortic regurgitation, serial monitoring of left ventricular dimensions and function is mandatory before and after valve replacement. Increasing systolic dimensions and decreasing contractility herald an impaired spontaneous course and should initiate aortic valve replacement. In uncomplicated cases, echocardiography gives sufficient information for operative decision making and quanti-tative left ventricular angiography is not needed. Within 6 months of valve replacement left ventricular dimen-sions become smaller in most patients. Persistence of severely increased left ventricular size is associated with impaired late postoperative survival. Future trials will have to show whether intensive medical treatment (i.e. ACE inhibitors) can improve long-term survival in patients who are at high risk. Other possible treatment options in patients with an unfavourable course are heart transplantation (when heart failure occurs) or ICD application (when severe rhythm problems arise).
References
[1] Borer JS, Hochreiter C, Herrold EM et al. Prediction of indications for valve replacement among asymptomatic or minimally symptomatic patients with chronic aortic regurgitation and normal left ventricular performance [see comments]. Circulation 1998; 97: 525–34.
[2] Spagnuolo M, Kloth H, Taranta A, Doyle E, Pasternack B. Natural history of rheumatic aortic regurgitation. Criteria predictive of death, congestive heart failure, and angina in young patients. Circulation 1971; 44: 368–80.
[3] Rapaport E. Natural history of aortic and mitral valve disease. Am J Cardiol 1975; 35: 221–7.
[4] Turina J, Hess O, Sepulcri F, Krayenbuehl HP. Spontaneous course of aortic valve disease. Eur Heart J 1987; 8: 471–83. [5] Braunwald E. Valvular heart diseases. In: Heart Disease,
5th edn. Philadelphia: W.B. Saunders Co, 1997: 1007–76. [6] Hegglin R, Scheu H, Rothlin M. Aortic insufficiency.
Circulation 1968; 38 (1 Suppl): 77–92.
[7] Nishimura RA, McGoon MD, Schaff HV, Giuliani ER. Chronic aortic regurgitation: indications for operation — 1988. Mayo Clin Proc 1988; 63: 270–80.
[8] Bonow RO, Epstein SE. Is preoperative left ventricular func-tion predictive of survival and funcfunc-tional results after aortic valve replacement for chronic aortic regurgitation? J Am Coll Cardiol 1987; 10: 713–6.
[9] Turina J, Turina M, Rothlin M, Krayenbuehl HP. Improved late survival in patients with chronic aortic regurgitation by earlier operation. Circulation 1984; 70 (Suppl I): I147–52. [10] Bonow RO, Picone AL, McIntosh CL et al. Survival and
functional results after valve replacement for aortic regurgi-tation from 1976 to 1983: impact of preoperative left ventricu-lar function. Circulation 1985; 72: 1244–56.
[11] Greves J, Rahimtoola SH, McAnulty JH et al. Preoperative criteria predictive of late survival following valve replacement for severe aortic regurgitation. Am Heart J 1981; 101: 300–8. [12] Borow KM, Green LH, Mann T et al. End-systolic volume as a predictor of postoperative left ventricular performance in volume overload from valvular regurgitation. Am J Med 1980; 68: 655–63.
[13] Henry WL, Bonow RO, Borer JS et al. Observations on the optimum time for operative intervention for aortic regurgi-tation. I. Evaluation of the results of aortic valve replacement in symptomatic patients. Circulation 1980; 61: 471–83. [14] Stone PH, Clark RD, Goldschlager N, Selzer A, Cohn K.
Determinants of prognosis of patients with aortic regurgi-tation who undergo aortic valve replacement. J Am Coll Cardiol 1984; 3: 1118–26.
[15] Gaasch WH, Carroll JD, Levine HJ, Criscitiello MG. Chronic aortic regurgitation: prognostic value of left ventricular end-systolic dimension and end-diastolic radius/thickness ratio. J Am Coll Cardiol 1983; 1: 775–82.
[16] Daniel WG, Hood WP, Jr., Siart A et al. Chronic aortic regurgitation: reassessment of the prognostic value of pre-operative left ventricular end-systolic dimension and fractional shortening. Circulation 1985; 71: 669–80.
[17] Taniguchi K, Nakano S, Hirose H et al. Preoperative left ventricular function: minimal requirement for successful late results of valve replacement for aortic regurgitation. J Am Coll Cardiol 1987; 10: 510–8.
[18] Turina J, Milincic J, Seifert B, Turina M. Valve replacement in chronic aortic regurgitation. True predictors of survival after extended follow-up. Circulation 1998; 98 (Suppl II): II100–6; discussion II6–7.
[19] Teichholz LE, Kreulen T, Herman MV, Gorlin R. Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence of absence of asynergy. Am J Cardiol 1976; 37: 7–11. [20] Edmunds LH, Jr., Clark RE, Cohn LH, Grunkemeier GL,
Miller DC, Weisel RD. Guidelines for reporting morbidity and mortality after cardiac valvular operations. The American Association for Thoracic Surgery, Ad Hoc Liason Committee for Standardizing Definitions of Prosthetic Heart Valve Morbidity. Ann Thorac Surg 1996; 62: 932–5.
[21] Thompson R, Ahmed M, Seabra-Gomes R et al. Influence of preoperative left ventricular function on results of homograft replacement of the aortic valve for aortic regurgitation. J Thorac Cardiovasc Surg 1979; 77: 411–21.
[22] Bonow RO, Carabello B, de Leon AC, Jr. et al. Guidelines for the management of patients with valvular heart disease: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Valvular Heart Disease). Circulation 1998; 98: 1949–84. [23] Klodas E, Enriquez-Sarano M, Tajik AJ, Mullany CJ, Bailey KR, Seward JB. Aortic regurgitation complicated by ex-treme left ventricular dilation: long-term outcome after surgi-cal correction [see comments]. J Am Coll Cardiol 1996; 27: 670–7.
[24] Lindblom D, Lindblom U, Qvist J, Lundstrom H. Long-term relative survival rates after heart valve replacement. J Am Coll Cardiol 1990; 15: 566–73.
[25] Nitter-Hauge S, Abdelnoor M, Svennevig JL. Fifteen-year experience with the medtronic-hall valve prosthesis. A follow-up study of 1104 consecutive patients. Circulation 1996; 94 (Suppl II): II105–8.
[26] Abdulla AM, Frank MJ, Canedo MI, Stefadouros MA. Limitations of echocardiography in the assessment of left ventricular size and function in aortic regurgitation. Circulation 1980; 61: 148–55.
[27] Bonow RO, Dodd JT, Maron BJ et al. Long-term serial changes in left ventricular function and reversal of ven-tricular dilatation after valve replacement for chronic aortic regurgitation. Circulation 1988; 78 (Suppl I): 1108–20. [28] Carroll JD, Gaasch WH, Naimi S, Levine HJ.
Regres-sion of myocardial hypertrophy: electrocardiographic-echocardiographic correlations after aortic valve replacement in patients with chronic aortic regurgitation. Circulation 1982; 65: 980–7.
[29] Christakis GT, Weisel RD, David TE, Salerno TA, Ivanov J. Predictors of operative survival after valve replacement. Circulation 1988; 78 (Suppl II): I25–34.
[30] Vongpatanasin W, Hillis LD, Lange RA. Prosthetic heart valves. N Engl J Med 1996; 335: 407–16.
[31] Bonow RO, Nikas D, Elefteriades JA. Valve replacement for regurgitant lesions of the aortic or mitral valve in advanced left ventricular dysfunction. Cardiol Clin 1995; 13: 73–83. [32] Fioretti P, Roelandt J, Sclavo M et al. Postoperative
regres-sion of left ventricular dimenregres-sions in aortic insufficiency: a long-term echocardiographic study. J Am Coll Cardiol 1985; 5: 856–61.
[33] Boucher CA, Bingham JB, Osbakken MD et al. Early changes in left ventricular size and function after correction of left ventricular volume overload. Am J Cardiol 1981; 47: 991–1004.
[34] Starling MR, Kirsh MM, Montgomery DG, Gross MD. Mechanisms for left ventricular systolic dysfunction in aortic regurgitation: importance for predicting the functional response to aortic valve replacement. J Am Coll Cardiol 1991; 17: 887–97.
[35] Schon HR, Dorn R, Barthel P, Schomig A. Effects of 12 months quinapril therapy in asymptomatic patients with chronic aortic regurgitation. J Heart Valve Dis 1994; 3: 500–9.
